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Multiple cell populations generate macrophage progenitors in the early yolk sac

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Abstract

Yolk sac (YS) CSF1 receptor positive (CSF1R+) cells are thought to be the progenitors for tissue-resident macrophages present in various tissues. The YS progenitors for tissue-resident macrophages are referred to as erythroid–myeloid progenitors (EMPs). However, diverse types of hematopoietic progenitors are present in the early YS, thus it is not precisely known which type of hematopoietic cell gives rise to the CSF1R+ lineage. In this study, an analysis was conducted to determine when CSF1R+ progenitors appeared in the early YS. It showed that CSF1R+ cells appeared in the YS as early as embryonic day 9 (E9) and that the earliest hematopoietic progenitors that differentiate into CSF1R+ cells were found in E8. Since these progenitors possessed the capability to generate primitive erythroid cells, it was likely that primitive erythroid lineages shared progenitors with the CSF1R+ lineage. Mutual antagonism appears to work between PU.1 and GATA1 when CSF1R+ cells appear in the early YS. One day later (E9), multiple progenitors, including myeloid-restricted progenitors and multipotent progenitors, in the YS could immediately generate CSF1R+ cells. These results suggest that EMPs are not an exclusive source for the CSF1R+ lineage; rather, multiple hematopoietic cell populations give rise to CSF1R+ lineage in the early YS.

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Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

YS:

Yolk sac

E:

Embryonic day

EMP:

Erythroid-myeloid progenitor

CPDP:

Common primitive-definitive precursor

MRP:

Myeloid-restricted progenitor

BM:

Bone marrow

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Acknowledgements

We thank K Isono for laboratory management and Dr. SI Hayashi for helpful discussions.

Funding

This work was supported by the JSPS KAKENHI (no. 17K09950) to TY and the Takeda Science Foundation to TY.

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Authors and Affiliations

  1. Department of Stem Cell and Developmental Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Japan

    Chie Ito, Mari Hikosaka-Kuniishi, Hidetoshi Yamazaki & Toshiyuki Yamane

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  1. Chie Ito
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  2. Mari Hikosaka-Kuniishi
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  3. Hidetoshi Yamazaki
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  4. Toshiyuki Yamane
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Contributions

TY conceived the experiments; TY and CI designed and performed the experiments; TY and CI analyzed the data; TY, CI, and MHK contributed to conceptualization; HY contributed analysis tools; and TY wrote the paper with input from CI and MHK.

Corresponding author

Correspondence to Toshiyuki Yamane.

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The authors declare no commercial or financial conflict of interest.

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All animal experiments are approved by the institutional review board of Mie University (permission nos. 20–22 and 2021–20). This article does not contain any studies with human participants.

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Ito, C., Hikosaka-Kuniishi, M., Yamazaki, H. et al. Multiple cell populations generate macrophage progenitors in the early yolk sac. Cell. Mol. Life Sci. 79, 159 (2022). https://doi.org/10.1007/s00018-022-04203-7

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  • DOI: https://doi.org/10.1007/s00018-022-04203-7

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